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Updated: May 19, 2026

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Published on: February 10, 2022
The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation
Ranita Ghosh Dastidar1, Jagmohan Hooda1, Ajit Shah1
1Department of Molecular and Cell Biology, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11 800 W Campbell Road, Richardson, TX, 75080, USA.
Background:
Hypoxia is associated with many disease conditions in humans, such as cancer, stroke and traumatic injuries. Hypoxia elicits broad molecular and cellular changes in diverse eukaryotes. Our recent studies suggest that one likely mechanism mediating such broad changes is through changes in the cellular localization of important regulatory proteins. Particularly, we have found that over 120 nuclear proteins with important functions ranging from transcriptional regulation to RNA processing exhibit altered cellular locations under hypoxia. In this report, we describe further experiments to identify and evaluate the role of nuclear protein relocalization in mediating hypoxia responses in yeast.
Results:
To identify regulatory proteins that play a causal role in mediating hypoxia responses, we characterized the time courses of relocalization of hypoxia-altered nuclear proteins in response to hypoxia and reoxygenation. We found that 17 nuclear proteins relocalized in a significantly shorter time period in response to both hypoxia and reoxygenation. Particularly, several components of the SWI/SNF complex were fast responders, and analysis of gene expression data show that many targets of the SWI/SNF proteins are oxygen regulated. Furthermore, confocal fluorescent live cell imaging showed that over 95% of hypoxia-altered SWI/SNF proteins accumulated in the cytosol in hypoxic cells, while over 95% of the proteins were nuclear in normoxic cells, as expected.
Conclusions:
SWI/SNF proteins relocalize in response to hypoxia and reoxygenation in a quick manner, and their relocalization likely accounts for, in part or in whole, oxygen regulation of many SWI/SNF target genes.
Insights
Hypoxia causes nuclear proteins to change location. SWI/SNF proteins rapidly move to the cytosol during hypoxia, impacting gene regulation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Hypoxia, a condition of low oxygen, is linked to diseases like cancer and stroke.
- Cellular responses to hypoxia involve significant molecular and protein localization changes.
- Over 120 nuclear proteins alter their location under hypoxic conditions, affecting crucial cellular functions.
Purpose of the Study:
- To identify proteins critical for mediating cellular responses to hypoxia.
- To investigate the role of nuclear protein relocalization in hypoxia response.
- To evaluate the function of these relocalizing proteins in yeast models.
Main Methods:
- Characterizing the time course of nuclear protein relocalization under hypoxia and reoxygenation.
- Analyzing gene expression data to identify oxygen-regulated genes.
- Utilizing confocal fluorescent live cell imaging to track protein localization.
Main Results:
- Seventeen nuclear proteins showed rapid relocalization in response to both hypoxia and reoxygenation.
- Components of the SWI/SNF complex were identified as fast responders.
- Over 95% of SWI/SNF proteins shifted from the nucleus to the cytosol under hypoxia.
Conclusions:
- SWI/SNF proteins exhibit rapid relocalization dynamics in response to oxygen level changes.
- This dynamic relocalization is a key mechanism in regulating SWI/SNF target genes under varying oxygen conditions.
- The findings suggest SWI/SNF protein movement significantly contributes to the cellular adaptation to hypoxia.
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